gms | German Medical Science

Introduction: Cochlear ablation causes a total sensory deafferentation in the cochlear nucleus. Aiming to investigate the regeneration potential of the adult central auditory system, we first determined what fraction of the total number of synaptic contacts (active zones) in the anteroventral cochlear nucleus (AVCN) is attributable to primary sensory innervation and how many synapses remain after total unilateral cochlear ablation. Second, we attempted to identify the potential for a deafferentation-dependent synaptogenesis in this region of the adult mammalian brain. Rejecting synaptophysin as a dependable marker for primary sensory axon terminals, synaptic contact zones (SCZs) were ultrastructurally identified before and after deafferentation in tissue treated for ethanolic phosphotungstic acid (EPTA) staining. Tissue processing also included pre-embedding immunocytochemistry for gephyrin to identify inhibitory synapses, the growth-associated protein GAP-43, the neurotransmitter glutamate, and the acetylcholine-synthesizing enzyme choline acetyltransferase.

Results: Using the physical fractionator on EPTA stained sections, we counted 1.11±0.09 (S.E.M.) x 109 SCZs per microliter of AVCN tissue. Within 7 days of deafferentation, this number was reduced by 46%. Excitatory and inhibitory synapses were differentially affected on the side of deafferentation. The former were quickly reduced and partially replaced, the latter were reduced more slowly, resulting in a transient rise of the fraction of inhibitory synapses, only to decline below original levels thereafter. Synaptogenesis was inferred by the emergence of morphologically immature SCZs systematically associated with GAP-43 immunoreactivity, estimated to comprise a fraction of almost 30% of newly formed synapses in the total synaptic population present by ten weeks after sensory deafferentation.

Conclusion: There is a considerable potential of the central auditory system in the adult mammalian brain for synaptogenesis and network reorganization even without pharmacological manipulations. This potential might be exploited in the future to help rebalancing the system after hearing loss by diverse causes.